1.0 PERFORMANCE
QUALIFICATION TEST

Following
Performance Qualification studies shall be carried out to ensure the equipment
for proper operation and its ability to sterilize and depyrogenate the washed
vials at the set parameters, repeatedly & consistently.

·
Air Velocity measurement.

·
HEPA FILTER Integrity test by DOP / PAO Aerosol test.

·
Air flow pattern test.

·
Non-viable airborne particle
count test.

·
Heat Distribution studies.

·
Heat Penetration studies.

·
Endotoxin Challenge study.

To
qualify the test the equipment should fulfill the acceptance criteria described
in the individual test procedures. All instruments shall be calibrated before
starting and after completion of validation studies.

After
completion of the qualification tests all the data generated will be compiled
to evaluate ability of the sterilization and depyrogenation tunnel to sterilize
& depyrogenate different articles at the set operating parameters.

2.0 TEST CALIBRATION
EQUIPMENTS

S.
No

Equipment
Name

Equipment
I.D

Calibration
on

Calibration Due
on

Verified By

2.1 QUALIFICATION OF
THE EXECUTION TEAM:

The
execution team should be trained for execution of operation Qualification of
the equipment & Record should be maintained in Annexure 1

2.2.1 AIR VELOCITY
MEASUREMENT

2.2.1.1 OBJECTIVE

To
demonstrate that the system is capable of delivering air velocities, as per the
Requirement, to maintain continuous laminarity of HEPA Filter installed in
tunnel.

2.2.1.2EQUIPMENT
USED

Digital
Anemometer

2.2.1.3 METHOD

A)
This test shall be performed by a trained personal and training record shall be
attached with report.

B)
This test shall be performed at least 30 minute after the tunnel has been
Started Heater should be off.

C)
Measure Air velocity 6 inches below the filter at 5 locations (four corner
filter and one center), calculate the average velocity of air coming from
supply.

D)
Calculate the velocity of air coming from supply filter should be measured in Feet/min.

E)
Record the Data in Annexure II.

V1
V2

V3

V4
V5

Average velocity (A) = V1+V2+V3+V4+V5/5

A = Average

2.2.1.4 ACCEPTANCE CRITERIA

Average
velocity across HEPA Filter should be within the range of 90±20 Feet/min

Average
velocity across HEPA Filter in sterilization zone should be within the range of
150-200Feet/min

2.2.2 HEPA FILTERS
LEAKAGE TEST (DOP/PAO TEST)

2.2.2.1 OBJECTIVE

To verify
the integrity of HEPA FILTERS installed in the sterilization and depyrogenation tunnel.

2.2.2.2 TEST
APPARATUS

•
Aerosol Generator

•
Aerosol photometer

•
Compressed Air

2.2.2.3 METHOD

a)
Filter testing shall be performed only after operational air velocities have
been verified and adjust wherever necessary.

b)
Position the smoke generator and introduce (DOP/PAO) smoke into the stream of
the HEPA Filter. The concentration of (DOP/PAO) aerosol is 80-120µg per
liter of air.

c)
Programme the instrument at 100% concentration for upstream.

d)
Scan the downstream side of the HEPA with an appropriate photometer probe.

e)
The probe shall scan the entire filter face and frame at a position about 1
inch from the face of the filter.

f)
Scanning shall be done at the rate of 2 feet/minute.

g)
Record the observation in Annexure III

2.2.2.4 ACCEPTANCE CRITERIA

During
scanning percentage of DOP or PAO penetration
shown by photometer should not be more than 0.01% of the upstream
concentration through the filter media and should be zero through mounting
joints.

2.2.3 AIR FLOW
LAMINARITY:

2.2.3.1 OBJECTIVE

To
determine the air flow pattern of HEPA Filter installed in sterilization and depyrogenation tunnel

2.2.3.2 EQUIPMENT USED

Titanium
Tetra Chloride (Chemical Used).

Video
Camera.

2.2.3.3 METHOD

TITANIUM TETRA CHLORIDE

a)
Take the glass rod with cotton or sponge tied to it.

b)Dip
the rod in Titanium Tetra Chloride solution and place the stick at Downstream
of HEPA Filter.

c)
Check the air flow direction at the Downstream of the filter face.

d) Observe
& record the same with video camera.

2.2.3.4 ACCEPTANCE CRITERIA

The
stream of air should be unidirectional and non-turbulent upto working zone.

2.2.3.5 Record
the result in Annexure V

2.2.4 AIR BORNE
NON-VIABLE PARTICLE COUNT TEST

2.2.4.1 OBJECTIVE

To
establish that at different locations within the tunnel, a count size of
particles per cubic meter is within the limit.

a)The test should be perform only when the earlier test have been
performed (air velocity, filter integrity, air laminarity) and found to be
conforming to the requirement. The particle count test should be performed by
qualified and/ or trained personnel only.

b)
Calculate the number of location by the following formula

No. of
sampling location: NL=√A

Where:

NL=The
minimum number of sampling locations (Rounded up to a whole number)

The
system shall capable of achieving the desired cleanliness grade in the
subjected critical work locations in the tunnelas per
the designed specified
limit

CRITERIA

ACCEPTANCE

Non viable Air
particle count test

Maximum
number of permitted particles per cubic meter equal to or above

GRADE

≥
0.5 µm

≥5.0 µm

GRADE
A

3520

29

2.2.5 HEAT
DISTRIBUTION STUDY

2.2.5.1 OBJECTIVE

The objective of the
test is to ensure that:

The Sterilizing &
Depyrogenating Tunnel when operated with Empty Chamber is capable of producing
the temperature profiles as per the temperature set points set in the PLC of
the equipment. The temperature distribution is uniform throughout the
sterilization period.

Three run to be
performed to qualify the measurement of the temperature throughout the chamber
during the sterilization cycle.

2.2.5.2 Equipment Used

Data
Logger with Minimum 12 Probes duly calibrated.

2.2.5.3 METHOD

Record
the set parameters of the sterilization cycle to be operated during the test.
Suspend the probe in the chamber in different position in such a way that
probes don’t touch any metallic surface. Record the position of the probe in a
representative schematic manner.

Connect
the probes to suitable data logger, which can scan and print the actual
temperature observed at different locations with respect to time.

Operate
the Sterilizing & Depyrogenation Tunnel
Also start the data logger to record the actual temperatures with respect
to time.

After
completion of sterilization cycle switch off the data logger.

Collect
print out from the printer of Sterilizing & Depyrogenation Tunnel.

Download
the data from the data logger in the computer for the data analysis and
printing enclosed the printout obtained from the data logger.

2.2.5.4 ACCEPTANCE CRITERIA:

The
Temperature at each Temperature probe should be ≥300°Cduring
the cycle.

2.2.5.5 Observations and Results In Annexure VI

Record
the temperature at various locations

2.2.6 HEAT
PENETRATION STUDY

2.2.6.1 OBJECTIVE

Objective
of this test is to ensure that, heat is sufficiently penetrating into the
innermost portion of the Vial subjected for sterilization &
Depyrogenation to achieve desired temperature during the sterilization &
Depyrogenation cycle.

Loaded
chamber Heat penetration studies must be conducted for three consecutive cycles with temperature probes.

The
recovery of Endotoxin Concentration after exposing to Depyrogenation tunnel
should show more than 3 log reduction.

Three run
to be performed to qualify the measurement of the temperature
throughout the tunnel by seven (during the sterilization cycle).

2.2.6.2 EQUIPMENT USED

Data
Logger with 12 Probes duly calibrated.

2.2.6.3 METHOD

Conduct
the study with loaded chamber for three consecutive cycles with
temperature probes and Endotoxin vials.

Suspend
the 12 probes inside the vial and put into tunnel for Heat Penetration Study.

Record
the position of the probes in a representative schematic form.

Insert 9
Endotoxin Vials (Marked vials) having 10000 EU each along with the temperature
sensors.

Connect
the probes to suitable data logger, which can scan and print the actual
temperature observed at different locations with respect to time.

Operate
the Sterilizing & Depyrogenating Tunnel also start the data logger to
record the actual temperatures within the Sterilizing & Depyrogenating
Tunnel with respect to time.

BELT SPEED CAN BE CALCULATED BY USING THE FOLLOWING FORMULA:

(Vial diameter)2 × cos30o ×
washing machine output

Tunnel conveyor width

STERILIZATION HOLD TIME: Length
of sterilizing zone

Conveyor speed

2.2.6.4 ACCEPTANCE CRITERIA

Throughout
the dwell time, all temperature measured in the chamber is ≥
300°C. The recovery of endotoxin concentration after exposing in sterilization and depyrogenation should
show at least 3 log reduction.

3.0 ACCEPTANCE CRITERIA

S.No.

TEST
PERFORMED

ACCEPTANCE
CRITERIA

1.

Air
velocity test

Average
velocity across the HEPA filter should be within the range of 90 ± 20%
FPM.

2.

HEPA
Filter integrity testing

Leakage
in the filter should not be more than 0.01% and should be zero through
mounting joints.

3.

Air
flow pattern

Air
flow pattern should be unidirectional and non turbulent.

4.

Non
Viable particle counter

Acceptable
limit of

0.5µ
Particles is 3520 and 5.0µ is 29 in 1M3 of
air.

5.

Heat
distribution studies

Temperature
should be uniform throughout the cycle

6.

Heat
penetration studies

Should
show at least 3 log reduction after exposing

Sterilization
temperature

4.0 RESULT:

The
results obtained after execution of the protocol, will be
presented in the validation report. All results will be compared against
the acceptance criteria. Any deviation failure to meet these specifications
will be duly documented. A deviation indicates variance from the acceptance
criteria however, does not necessarily mean that the qualification as
unacceptable. During execution of this protocol, if any deviation is noticed,
the person executing the protocol initiates a deviation report and provides the
detail description of the deviation. Investigation may be performed to identify root cause for the deviations or failures and corrective action will be taken to minimize such deviations or failures in the
future.